Glomerular permeability and polyanion in adriamycin nephrosis in the rat

Alterations in glomerular permeability were studied in Adriamycin-induced proteinuria in rats by measuring fractional clearances (C/GFR) of uncharged labeled dextrans of varying molecular radii (ae) and of anionic, native, and cationic horseradish peroxidases (HRP) in experimental and control animals. Experimental animals were studied between days 14 and 55 after a single intravenous dose of Adriamycin (doxorubicin), 7.5 mg/kg. Mean proteinuria in the experimental animals was 98 mg/24 hr. Glomerular morphology showed few changes except for epithelial cell swelling, vacuolization, and foot process obliteration, and a significant reduction of glomerular colloidal iron staining. Polyethyleneimine staining revealed a similar distribution of anionic sites in the laminae rarae interna and externa in proteinuric rats as compared with controls. Inulin clearances revealed reduction in GFR and RPF of 20 and 15%, respectively. Dextran C/GFR values showed in experimental animals a size defect for molecules with an ae exceeding 40 A, with a four- to fivefold increase over the values found in control animals for dextrans with ae of 58 and 60 A. The peroxidase clearances showed a slight increase in C/GFR of anionic HRP in experimental animals, as could be expected on the basis of the sieving defect, whereas the C/GFR values for native and cationic HRP were virtually unchanged, indicating an intact functional charge barrier in the proteinuric animals.(ABSTRACT TRUNCATED AT 250 WORDS)